Angelica dahurica Extracts Improve Glucose Tolerance through the Activation of GPR119

• Published in: PloS one 2016-07, Vol.11 (7), p.e0158796-e0158796
• Main Authors: Park, Eun-Young, Kim, Eung-Hwi, Kim, Chul-Young, Kim, Mi-Hwi, Choung, Jin-Seung, Oh, Yoon-Sin, Moon, Hong-Sub, Jun, Hee-Sook
• Format: Article
• Language: English
• Subjects: Activation; Angelica; Angelica (Plant); Angelica - chemistry; Animals; Biology and Life Sciences; Cancer; Care and treatment; CHO Cells; Cricetinae; Cricetulus; Cyclic AMP; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Glucagon; Glucagon-like peptide 1; Glucose; Glucose tolerance; Glucose Tolerance Test; Herbal medicine; Humans; Hypoglycemia - drug therapy; Hypoglycemia - genetics; Hypoglycemia - metabolism; In vivo methods and tests; Insulin; Insulin resistance; Insulin secretion; Intestine; Intracellular; L cells; L Cells (Cell Line); Male; Medical research; Medicine and Health Sciences; Metabolism; Mice; n-Hexane; Pancreas; Penicillin; Peptides; Pharmacy; Physical Sciences; Physiological aspects; Plant extracts; Plant Extracts - chemistry; Plant Extracts - pharmacology; Properties; Proteins; Rats; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Rodents; Secretion; Therapeutic applications; Type 2 diabetes; Umbelliferae
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0158796

G protein-coupled receptor (GPR) 119 is expressed in pancreatic β-cells and intestinal L cells, and is involved in glucose-stimulated insulin secretion and glucagon-like peptide-1 (GLP-1) release, respectively. Therefore, the development of GPR119 agonists is a potential treatment for type 2 diabetes. We screened 1500 natural plant extracts for GPR119 agonistic actions and investigated the most promising extract, that from Angelica dahurica (AD), for hypoglycemic actions in vitro and in vivo. Human GPR119 activation was measured in GeneBLAzer T-Rex GPR119-CRE-bla CHO-K1 cells; intracellular cAMP levels and insulin secretion were measured in INS-1 cells; and GLP-1 release was measured in GLUTag cells. Glucose tolerance tests and serum plasma insulin levels were measured in normal C57BL6 mice and diabetic db/db mice. AD extract-treated cells showed significant increases in GPR119 activation, intracellular cAMP levels, GLP-1 levels and glucose-stimulated insulin secretion as compared with controls. In normal mice, a single treatment with AD extract improved glucose tolerance and increased insulin secretion. Treatment with multiple doses of AD extract or n-hexane fraction improved glucose tolerance in diabetic db/db mice. Imperatorin, phellopterin and isoimperatorin were identified in the active fraction of AD extract. Among these, phellopterin activated GPR119 and increased active GLP-1 and insulin secretion in vitro and enhanced glucose tolerance in normal and db/db mice. We suggest that phellopterin might have a therapeutic potential for the treatment of type 2 diabetes.